Abstract. Pathology of the cardiovascular system occupies a major place in the structure of diseases of the elderly and old patients. Metabolic disturbances are very important in ischemic damages of myocardium in the elderly and old people. So, drugі with metabolic mechanism of action is very ppromising in the treatment of elderly patients with cardiovascular diseases. The relevance of this study is determined by the feasibility of using drugs of metabolic action, which have a beneficial effect on the metabolism of cardiomyocytes, improve blood supply to the myocardium, increase its contractile function. The effect of ATP-molsidomine combination on myocardial contractility in different age animals was stuiesy in vitro experiments. The experiments on the isolated hearts from adult and old rats have shown that combined use of ATP and molsidomine did not significantly affect the contractility of the isolated hearts of adult rats under different perfusion regimes. In old rats, the use of ATP-molsidomine combination had a positive effect on the contractile function of the myocardium under the influence of damaging factors (ischemia, reperfusion): prevented a decrease of left ventricular developing pressure and its first derivative (velocity of pressure rise and velocity of pressure decline) and accelerated its growth during reperfusion. Co-administration of ATP and molsidomine during ischemia had a positive effect on the heart rhythm and restored heart rate at the reperfusion period in adult and old rats. The results of the study indicate a positive effect of the ATP-molsidomine combination on the myocardial contractility in old rats. Combined use of ATP and molsidomine exerted a favourable influence on the heart rhythm under damaging factors both in the adult and old animals. Key words: ATP; molsidomine; isolated rat heart; myocardial contractility; ageing

Adaptive reactions to chronic stress, reaching a certain intensity, can become harmful and be involved in any pathological process. Therefore, the search for new ways to increase the adaptive capacity reduced with age and the body's resistance to the negative effects of chronic stress remains relevant. The aim of the study was to experimentally study the age-related protective properties of the combination of molsidomine and ATP in chronic mild stress. The experiments were performed on young (6 months) and old (26 months) Wistar rats exposed to stressors that changed periodically at random for 8 weeks. During the 6-8th week of the experiment, against the background of stress, the animals were sublingually administered a pharmacological combination based on molsidomine - 2 mg / kg, ATP - 10 mg / kg. It was found that the adaptive reactions of young and old animals to chronic stress have qualitative and quantitative differences. Chronic stress in old rats caused changes in behavior and psycho-emotional state, deterioration of cognitive function, changes in lipoperoxidation. On the part of the immune system in old rats, against the background of a pronounced age involution of lymphoid organs, no significant changes in thymus mass and cellularity were observed during chronic stress, while the mass and cellularity of the spleen increased. The combination of molsidomine and ATP prevented post-stress changes in animal behavior, reduced anxiety, normalized social activity, restored the lost ability to recognize, improved cognitive function. The drug contributed to the preservation of the function of immunocompetent organs in young animals and to a lesser extent showed a protective effect in older animals against the background of involutional changes caused by both aging and chronic stress. The combination of molsidomine and ATP had an antioxidant effect. Thus, in chronic mild stress, older animals showed a different response from young animals to both stress and the administration of molsidomine with ATP. The applied pharmacological combination can be considered as a promising stress-protective agent that has a complex effect on various pathogenetic links of chronic stress due to its neuro- and immunomodulatory, energy-saving, antioxidant properties. Keywords: aging, chronic stress, anxiety, social activity, cellularity of the thymus and spleen, lipid peroxidation, combination of molsidomine and ATP, pharmacological action.

Stressful situations that accompany us during military operations provoke a significant increase in the incidence of cardiovascular and psychoneurological pathology, especially among the elderly. Therefore, there is a need for a complex approach to treatment, in particular, with the use of combined drugs. The review presents data from preclinical and clinical studies on drugs with metabolic action - meldonium (trimethylhydrazinium propionate), L-arginine, and inosine. It has been shown that, apart from the general pharmacotherapeutic action, these drugs have a significant clinical effect on various illnesses in the form of adjunctive therapy. Antioxidant, neuroprotective, vasodilatory, and several pleiotropic effects of meldonium have been established. The use of meldonium as part of combined therapy improves the prognosis in cardiovascular and neurological disease treatment. Most reports ascribe the clinical benefits of L-arginine in cardiovascular diseases to the provision of NO. L-arginine is the only precursor for the NO-synthase reaction. NO is produced by all tissues of the body and plays particularly important roles in cardiovascular homeostasis. Very few articles examine the effects of L-arginine supplementation on central nervous system (CNS) function. However, accumulating evidence indicates that NO plays a role in memory formation. The possible role of L-arginine in Alzheimer's disease was investigated, taking into account the known functions of L-arginine in atherosclerosis, redox stress and inflammation, regulation of synaptic plasticity and neurogenesis, as well as modulation of glucose metabolism and insulin activity. Evidence is provided that L-arginine may play a prominent role in protecting against age-related degenerative diseases such as Alzheimer's disease. L-arginine has been demonstrated to improve peripheral circulation, renal function, and immune function. It also possesses anti-stress and adaptogenic capabilities. L-arginine stimulates the release of growth hormone as well as the release of pancreatic insulin and glucagon and pituitary prolactin. The antioxidant property of L-arginine has been well documented in several reports. As well known that inosenhancesance the myocardial energy potential improvesrove coronary circulation. At the same time over the past two decades, inosine has been shown to evoke significant improvements in motor function and visceral organ control in preclinical models of neurologic injury including spinal cord injury, stroke, traumatic brain injury, multiple sclerosis, and Parkinson`s disease through its ability to enhance the growth of axon collaterals from undamaged neurons. The basis of these beneficial effects stems from its antioxidant, anti-inflammatory, anxiogenic and neuroprotective properties. Keywords: age-related pathology; combined drugs; meldonium; L-arginine; inosine, endothelial dysfunction.

Brain aging is accompanied by the development of an imbalance of the systems of chemical regulation of cells, a decrease in neurotrophic factors, and disorders of brain plasticity. Important place in the neurotransmitter changes in aging is given to the γ-aminobutyric acid (GABA), represented in the system of both external and internal neurotransmitters. With aging, the activity of GABA systems changes and the content of GABA in brain structures decreases, which is associated with impaired mental function and the development of pathology, in particular, dementia. Given the prevalence of pathology and the rate of population aging, the search for effective and safe means for the prevention and comprehensive metabolic treatment of age-related cognitive and psycho-emotional disorders remains relevant. In experiments on adult (10 months) and old (24 months) Wistar male rats, we investigated the pharmacological activity and age-specificities of the combination, including GABA and magnesium gluconate in the form of a coordination compound (γ-aminobutyro-Mg(II)–gluconate), and pyridoxine hydrochloride (Membraton). Tests "dark / light camera" and "three-chamber activity" established age differences in the behavior of rats. In older animals, amid increased anxiety, there was a decrease in zoo social interaction, such as communication, novelty preference, and social recognition. Under the influence of the course introduction of Membraton (100 and 500 mg / kg) in old rats, anxiety decreased and social activity increased: motivation and initiation of social contact increased, contact with an unfamiliar partner-stimulus increased, recognition of a familiar and unfamiliar partner was normalized. Under the influence of the remedy, indicators of social behavior of old animals approached the level of young animals. The established effects make it possible to consider Membraton as a promising metabolic therapy for increasing sociality in psycho-emotional disorders associated with age.

Vasodilatory activity of high density lipoproteins and the content of apolipoprotein A-I in these particles decreases in senescent rats in comparison with adult animals. Implantation of human apolipoprotein A-I gene increases the content of this apolipoprotein in high density lipoproteins and improves their vasodilatory effect. Key Words: gene; lipoproteins; vessels; agingChanges in the content and proportion between various circulating lipoprotein complexes (dyslipoprotei~ nemias) can modulate metabolic and functional alterations in the cardiovascular system during aging and atherosclerosis development [ 1,5]. Lipoprotein (LP) classes differ in their acceptor and transporting functions, while functional properties of different LP depend on their apoprotein constituents [7]. In particular, antiatherogenic properties of high density lipoproteins (HDL) are determined by the presence of apolipoprotein (apo) A-I.LP complexes act as effective regulators of vascular reactivity [ 11]. We previously demonstrated that vasoactive effects of LP decrease during aging [4]. It was shown that implantation of human apo-A-I gene to rats modulates plasma content of different LP classes in senescent animals [3].In light of this it was interesting to study agerelated differences in the effect of implanted human